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Background: A California-based health plan offered home-based palliative care (HBPC) to members who needed support at home but did not yet qualify for hospice. Objectives: This study compares hospital and emergency department (ED) utilization and costs and mortality for individuals receiving HBPC to a cohort not receiving palliative care services (Usual Care). Design: This is an observational retrospective study using claims data covering a prestudy period and a study period during which time half of the study population received HBPC services. Setting/Subjects: Seriously ill individuals who received HBPC were matched with those receiving Usual Care using a propensity-based matching algorithm. Intervention: Interdisciplinary teams from home health and hospice agencies provided HBPC services. Measurements: Outcome measures included hospital and ED utilization and cost before and during the study period and mortality during the study period. Results: For both groups, hospital and ED utilization and associated costs were higher during the prestudy period than during the study period. No differences were found in outcome measures between groups during the study period. Average time in the study period was longer for the HBPC group than that in the Usual Care group, indicating that they lived longer or transitioned to hospice later. Conclusion: Although individuals in both groups were living with serious illnesses for which worsening health and increased acute care utilization are expected over time, both groups had reduced acute care utilization and costs during the study period compared with the prestudy period. Reduced utilization and costs were equivalent for both groups. [ABSTRACT FROM AUTHOR]

Background: Rady Children's Hospital (RCH) offers an outpatient pediatric palliative clinic that began offering telepalliative care in 2016. Objectives: This study describes demographics of parents receiving pediatric telepalliative care, patient/family satisfaction with telepalliative care, and patient/family perspectives. Design: Retrospective electronic medical record chart review (2016–2020) of telepalliative patients at RCH (San Diego, USA), including satisfaction surveys. Documented quotes from telepalliative care consultations were analyzed thematically. Results: Fifty-six patients were seen through 181 telepalliative visits. Demographics: Forty-three percent were female and 32% were Hispanic/Latino. Ages ranged from 3 months to 25 years. Average Palliative Performance Scale was 47%. Seventy-nine percent used gastrostomy tubes for nutrition, but only 29% used home ventilation. Eighty-two percent completed a Physician Order for Life-Sustaining Treatment. Goals for 84% of patients were for life prolongation and attempt resuscitation. Visits averaged 86 minutes. Twenty-five surveys were returned: 92% felt very satisfied and 96% said the video visit was the same, better, or much better than an in-person visit. Sixty-four percent said the video visit was more convenient and 68% felt the video visit was safer. Identified themes from telepalliative consultations included advocacy for their child, challenges surrounding care for children with complex medical needs, medical team communication, caregiver support, facing uncertainty, and decision making. Conclusions and Implications: Pediatric patients receiving telepalliative care varied in demographics, functional status, and goals of care. Telepalliative care can provide good quality of care and patient satisfaction. In a telepalliative setting, parents were able to communicate challenging aspects of care including navigating uncertainty, finding support, and decision making. [ABSTRACT FROM AUTHOR]

Abstract Background Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. Results C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7ErbB2) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130Cas/JNK interaction. Conclusions C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is an interferon-induced protein kinase that plays a central role in the anti-viral process. Due to its pro-apoptotic and anti-proliferative action, there is an increased interest in PKR modulation as an anti-tumor strategy. PKR is overexpressed in breast cancer cells; however, the role of PKR in breast cancer cells is unclear. The expression/activity of PKR appears inversely related to the aggressiveness of breast cancer cells. The current study investigated the role of PKR in the motility/migration of breast cancer cells. The activation of PKR by a synthesized dsRNA (PIC) significantly decreased the motility of several breast cancer cell lines (BT474, MDA-MB231 and SKBR3). PIC inhibited cell migration and blocked cell membrane ruffling without affecting cell viability. PIC also induced the reorganization of the actin cytoskeleton and impaired the formation of lamellipodia. These effects of PIC were reversed by the pretreatment of a selective PKR inhibitor. PIC also activated p38 mitogen-activated protein kinase (MAPK) and its downstream MAPK-activated protein kinase 2 (MK2). PIC-induced activation of p38 MAPK and MK2 was attenuated by the PKR inhibitor and the PKR siRNA, but a selective p38 MAPK inhibitor (SB203580) or other MAPK inhibitors did not affect PKR activity, indicating that PKR is upstream of p38 MAPK/MK2. Cofilin is an actin severing protein and regulates membrane ruffling, lamellipodia formation and cell migration. PIC inhibited cofilin activity by enhancing its phosphorylation at Ser3. PIC activated LIM kinase 1 (LIMK1), an upstream kinase of cofilin in a p38 MAPK-dependent manner. We concluded that the activation of PKR suppressed cell motility by regulating the p38 MAPK/MK2/LIMK/cofilin pathway. [ABSTRACT FROM AUTHOR]

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanolinduced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanolinduced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanolinduced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47phox and p67phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47phox and p67phox, which were prerequisites for NOX assembly and activation. Knocking down p47phox with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanolmediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation. Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation. These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons. [ABSTRACT FROM AUTHOR]

Background: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. Results: C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7ErbB2) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130Cas/JNK interaction. Conclusions: C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis. [ABSTRACT FROM AUTHOR]